Cells of the innate immune system Flashcards
Eosinophils: abundancy, how they stain, granules, rxns, proteins produced
2-5% of white blood cells stain red-pink granules: basic proteins, peroxidases, antimicrobial substances involved in EXTRACELLULAR digestion inflammatory mediators
Mast cells are
tissue fixed
basophils are
circulating in the blood
mast/basophils play a role in what awful rxn?
anaphalactic rxns?
Basophils stain
purple-black
basophil granules contain
histamine, serotonin, heparin
cytokines, chemokines
Macrophages do what
phagocytes and APCs
In connective tissue macs are called
histocytes
In the liver macs are called
kupfer cells
in the alveolar cells they are called
alveolar macs
in the CNS they are called
microglial cells
Macrophage
1) produce and release: _____ enzymes
2) produce and release: _____ inflammatory mediators
1) lipases/galactosidases
2) cytokines/chemokines
3) ROI
4) NO
NK cells
what causes them to destroy?
what are their targets?
What kind of Ag receptor?
1) they dont need prior stimulation
2) cancer cells, viral infected cells, transplant cells
3) no specific AG receptor
What mechanism allows innate immunity to discriminate self/nonself?
PAMPs via PRRs
PRRs: properties
recognize mannose-tails, essential property of surface molecules of bacteria and viruses
germ-line encoded (limited diversity)
nonclonal: identical on all cells
discriminate self/non-self
TLRs do what “ultimately” ?
recognize PAMPs and activate inflammation
TLRs do what specifically
they cause the formation of transcription factors
NF-kB and IRFs.
NF-KB –> acute inflammation
IRFs –> IFN alpha/beta
TLRs—> MyD88 adaptor –>
IRAK enzymes –> TRAF (goes two ways)
- ---> inactivation of IkB --> NFkB
- ---> induction of MAPK kinases
- ---> pro-inflammatory genes
TLR-4
Sequence of events leading to cytokine production
Step 1
TLR-4, co-receptor CD14, MD2, and LPS form a complex
CD14 grabs LPS, whose tail interacts on MD2 on TLR-4
TLR-4
Sequence of events leading to cytokine production
Step 2
TIR domain intracellularly binds to MyD88
MyD88’s death domain interacts with death domain of IRAK4
this causes TRAF-6 to bind IKK
IKK binds IkB, NF-kB
TLR-4
Sequence of events leading to cytokine production
Step 3
NF-kB activates transcription of genes –> inflammation
name all the proteins and their functions in TLR-4 LPS recognition
TLR-4
MD2- the bridge between TLR-4-MD2-LPS-CD14
LPB
LPS binding protein in the blood
TIR domain
Toll/Interleukin-1 receptor associated kinase 4
domain on the cytoplasmic side of TLR -4
IRAK-4
interleukin 1 receptor associated kinase 4
IKK
I kappa B kinase
how do PRRs work?
receptor recognizes pathogen, phagocytosis occurs, lysosome fuses with phagocyte, kills microbe
interiorly, iNOS or phagocyte oxidase produces NO and ROS
Complement:
consists of ? what is their normal state?
what happens during activation?
what do the large fragments forms versus the small fragments?
1) serum proteins
2) soluble inactive precursors
3) they are cleaved
4) large form the membrane attack complex
5) small form
a) chemoattractants
b) anaphylatoxins
c) opsonins
the large fragment has two sites
enzyme site and attachment site
what pathways does complement activation have
Classical: Ab mediated
Alternative: Ab independent, microbial cell wall activating
lectin: MBL binds microbial carbohydrates in the plasma
CAL
Alt-Mic-MBL
what pathway forms MAC?
lytic pathway
Classical PW overview C3—>
C3b, associates with C2a, which associate with C4b linked to a bacterium
C3bC2aC4b = C5 convertase
C5 Con. —> C5 —> C5b and C5a
C5b + C6, 7, 8, 9 = MAC
Acute phase proteins
circulating proteins, induced rapidly by cytokines after infection
these include MBL and C-reactive protein (CRP)
MBL
recognizes microbial carbohydrates, activates lectin pathway
CRP
binds to phosphorylcholine on microbes and coats the microbes for phagocytosis by macrophages
